AzTrials
AzTrials

Locally Advanced or Metastatic Solid TumorsPhase 2NCT02478099

MPDL3280A-treatment-IST-UMCG

A Phase 2 study testing MPDL3280A in people with Locally Advanced or Metastatic Solid Tumors, run by University Medical Center Groningen at 1 site in Netherlands.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
Search all trials

Trial summary

To be able to evaluate the investigational imaging - 89Zr-MPDL3280A-PET, 89Zr-CD8 imaging and 18F-FB-IL2-PET - as complementary tools for selection of patients to be treated with MPDL3280A, within this treatment trial the investigators will assess safety, tolerability and anti-tumor activity of MPDL3280A in cancer… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
MPDL3280A
Could I receive a placebo?
No, everyone receives an active treatment
How many people
81 participants
Where
1 siteNetherlands
Study dates
24 Feb 2016to Jul 2024
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically or cytologically documented locally advanced or metastatic solid tumor, whom in the opinion of the investigator, based on available clinical data, may benefit from treatment with anti PD-L1 immunotherapy .
  • Participation within the 18F-IL2 imaging trial (IL2-img-UMCG-2015) or 89Zr-MPDL3280A antibody imaging trial (MPDL3280A-img-042015) or CD8 imaging trial (ZED88082-img-UMCG-2018) before participation in the MPDL3280A treatment trial.
  • Subject must have undergone a fresh tumor biopsy for PD-L1 assessment performed as part of one of the investigational imaging trials.
  • Subjects are eligible if disease progression during or following first-line chemotherapy or any subsequent treatment lines for locally advanced or metastatic solid tumor whom, in the opinion of the investigator, based on available clinical data, may benefit from treatment with anti PD-L1 immunotherapy .
  • ● Additional criteria for cancer of the urinary tract:
  • Subjects with disease progression during or following platinum-based adjuvant/neoadjuvant chemotherapy are eligible if ≤ 12 months have elapsed between the last treatment administration and the date of recurrence.
Show all 29Show fewer
  • ● Additional criteria for NSCLC:
  • Subjects with disease progression during or following platinum-based adjuvant/neoadjuvant chemotherapy or concurrent chemoradiation for NSCLC are eligible if ≤ 6 months have elapsed between the last treatment administration and the date of recurrence.
  • Subjects with a known sensitizing mutation in the epidermal growth factor receptor (EGFR) gene must also have experienced disease progression (during or after treatment) or intolerance to treatment with erlotinib, gefitinib, or another EGFR tyrosine kinase inhibitor (TKI).
  • Subjects with a known Anaplastic Lymphoma Kinase (ALK) fusion oncogene must also have experienced disease progression (during or after treatment) or intolerance to treatment with crizotinib or another ALK inhibitor.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Life expectancy ≥12 weeks.
  • Signed Informed Consent Form.
  • Ability to comply with protocol.
  • Age ≥18 years.
  • Measurable disease, as defined by standard RECIST v1.1. Previously irradiated lesions should not be counted as target lesions.
  • Adequate hematologic and end organ function, defined by the following laboratory results obtained within ≤28 days prior to the first full dose of MPDL3280A:
  • ANC ≥1500 cells/μL (without granulocyte colony-stimulating factor support within 2 weeks prior to Cycle 1, Day 1).
  • WBC counts >2500/μL.
  • Lymphocyte count ≥500/μL.
  • Platelet count ≥100,000/μL (without transfusion within 2 weeks prior to Cycle 1, Day 1).
  • Hemoglobin ≥9.0 g/dL. Subjects may be transfused or receive erythropoietic treatment to meet this criterion.
  • AST, ALT, and alkaline phosphatase ≤ 2.5× the upper limit of normal (ULN), with the following exceptions:
  • Subjects with documented liver metastases: AST and/or ALT ≤ 5 × ULN.
  • Subjects with documented liver or bone metastases: alkaline phosphatase ≤ 5 × ULN.
  • Serum bilirubin ≤ 1.5 × ULN. Subjects with known Gilbert disease who have serum bilirubin level ≤ 3 × ULN may be enrolled.
  • INR and aPTT ≤ 1.5 × ULN. This applies only to subjects who are not receiving therapeutic anticoagulation; subjects receiving therapeutic anticoagulation should be on a stable dose.
  • Creatinine clearance ≥ 30 mL/min
  • For female subjects of childbearing potential and male subjects with partners of childbearing potential, agreement (by subject and/or partner) to use a highly effective form(s) of contraception (i.e., one that results in a low failure rate [< 1% per year] when used consistently and correctly) and to continue its use for 6 months after the last dose of MPDL3280A.

Who cannot join

  • Any approved anti-cancer therapy, including chemotherapy or hormonal therapy within ≤21 days prior to the first full dose of MPDL3280A; the following exceptions are allowed:
  • Hormone-replacement therapy or oral contraceptives.
  • TKIs approved for treatment of NSCLC discontinued >7 days prior to the first full dose of MPDL3280A. The baseline scan must be obtained after discontinuation of prior TKIs.
  • Treatment with any other investigational agent, other than the investigational tracer 89Zr-MPDL3280A, 18F-FB-IL2 or 89Zr-CD8-imaging, or participation in another clinical trial with therapeutic intent within 28 days prior to the first full dose of MPDL3280A.
  • Unstable brain metastases.
  • Unstable leptomeningeal disease.
Show all 50Show fewer
  • Uncontrolled tumor-related pain.
  • Subjects requiring pain medication must be on a stable regimen at study entry.
  • Symptomatic lesions amenable to palliative radiotherapy (e.g., bone metastases or metastases causing nerve impingement) should be treated prior to enrollment. Subjects should be recovered from the effects of radiation. There is no required minimum recovery period.
  • Asymptomatic metastatic lesions whose further growth would likely cause functional deficits or intractable pain (e.g., epidural metastasis that is not currently associated with spinal cord compression) should be considered for loco-regional therapy if appropriate prior to enrollment.
  • Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently). Subjects with indwelling catheters (e.g., PleurX) are allowed.
  • Uncontrolled hypercalcemia (> 1.5 mmol/L ionized calcium or calcium >12 mg/dL or corrected serum calcium >ULN) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab.
  • Subjects, who are receiving bisphosphonate therapy or denosumab specifically to prevent skeletal events and who do not have a history of clinically significant hypercalcemia are eligible.A second malignancy within 5 years prior to Cycle 1 Day 1, with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated with curative intent, ductal carcinoma in situ treated surgically with curative intent).
  • Pregnant and lactating women.
  • History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins.
  • Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cell products or any component of the MPDL3280A formulation.
  • History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis.
  • Subjects with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible for this study.
  • Subjects with controlled Type I diabetes mellitus on a stable dose of insulin regimen may be eligible for this study.
  • Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions:
  • Rash must cover less than 10% of body surface area (BSA).
  • Disease is well controlled at baseline and only requiring low potency topical steroids.
  • No acute exacerbation of underlying condition within the previous 12 months (not requiring PUVA [psoralen plus ultraviolet A radiation], methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, high potency or oral steroids).
  • History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.
  • History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
  • Serum albumin < 2.5 g/dL.
  • Positive test for HIV.
  • Subjects with active hepatitis B (chronic or acute; defined as having a positive hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C.
  • Subjects with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as the presence of hepatitis B core antibody [HBcAb] and absence of HBsAg) are eligible. HBV DNA test must be performed in these subjects prior to Cycle 1, Day 1.
  • Subjects positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
  • Active tuberculosis.
  • Severe infections within 4 weeks prior to the first full dose of MPDL3280A, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia.
  • Signs or symptoms of infection within 2 weeks prior to Cycle 1, Day 1.
  • Received therapeutic oral or IV antibiotics within 2 weeks prior to Cycle 1, Day 1.
  • ● Subjects receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or to prevent chronic obstructive pulmonary disease exacerbation) are eligible.
  • Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within the previous 3 months, unstable arrhythmias, or unstable angina.
  • ● Subjects with known coronary artery disease, congestive heart failure not meeting the above criteria, or left ventricular ejection fraction <50% must be on a stable medical regimen that is optimized in the opinion of the treating physician, in consultation with a cardiologist if appropriate.
  • Major surgical procedure other than for diagnosis within 28 days prior to Cycle 1, Day 1 or anticipation of need for a major surgical procedure during the course of the study.
  • Prior allogeneic bone marrow transplantation or solid organ transplant.
  • Administration of a live, attenuated vaccine within 4 weeks before Cycle 1, Day 1 or anticipation that such a live attenuated vaccine will be required during the study.
  • ● Influenza vaccination should be given during influenza season only (example: approximately October to March in the Northern Hemisphere). Subjects must not receive live, attenuated influenza vaccine (e.g. FluMist®) within 4 weeks prior to Cycle 1, Day 1 or at any time during the study treatment of within 5 months after the last dose of MPDL3280A.
  • Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the subject at high risk from treatment complications.
  • Prior treatment with CD137 agonists or immune checkpoint blockade therapies, anti-PD-1, and anti-PD-L1 therapeutic antibodies.
  • ● Subjects who have had prior anti-CTLA-4 treatment may be enrolled, provided the following requirements are met:
  • Minimum of 6 weeks from the last dose of anti-CTLA-4
  • No history of severe immune related adverse effects from anti-CTLA-4 (CTCAE Grade 3 and 4)
  • Treatment with systemic immunostimulatory agents (including but not limited to IFNs, IL-2) within 6 weeks or five half-lives of the drug, whichever is shorter, prior to the first full dose of MPDL3280A.
  • Treatment with systemic immunosuppressive medications (including but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents) within 2 weeks prior to Cycle 1, Day 1.
  • Subjects who have received acute, low-dose, systemic immunosuppressant medications (e.g. a one-time dose of dexamethasone for nausea) may be enrolled in the study after discussion with and approval by the sponsor.
  • The use of inhaled corticosteroids for chronic obstructive pulmonary disease, mineralocorticoids (e.g. fludrocortisone) for subjects with orthostatic hypotension, and low-dose supplemental corticosteroids for adrenocortical insufficiency are allowed.

Trial locations and contacts

1 site in 1 country.

Netherlands1 site

  • University Medical Center Groningen

    Groningen, 9713 GZ

Other trials in Netherlands

About this study

Official title: MPDL3280A Treatment in Patients With Locally Advanced or Metastatic Solid Tumors After or During Investigational Imaging

To be able to evaluate the investigational imaging - 89Zr-MPDL3280A-PET, 89Zr-CD8 imaging and 18F-FB-IL2-PET - as complementary tools for selection of patients to be treated with MPDL3280A, within this treatment trial the investigators will assess safety, tolerability and anti-tumor activity of MPDL3280A in cancer patients, who have undergone investigational imaging.

Read the detailed description

Encouraging clinical data emerging in the field of tumor immunotherapy have demonstrated that therapies focused on enhancing T cell responses against cancer can result in a significant survival benefit in patients with Stage IV cancer. PD-L1 is an extracellular protein that downregulates immune responses primarily in peripheral tissues through binding to its two receptors PD-1 and B7-1. Interruption of the PD L1/PD-1 pathway by the PD-L1 targeting antibody MPDL3280A, represents an attractive strategy to reinvigorate tumor-specific T cell immunity. For PD1/PD-L1 pathway inhibition PD-L1 tumor surface expression was proposed as a potential biomarker. In early clinical trials, PD-L1 expression has been associated with response to PD1/PD-L1 inhibition. However, other clinical trials reported response to PD1/PD-L1 checkpoint inhibitors in a big patient groups who were PD-L1-negative assessed by a single biopsy. Another obstacle to using PD-L1 expression as predictive biomarker might be its potential heterogeneous expression and fast dynamics PD-L1 tumor expression and whole body distribution, as well as baseline activation status of the immune system are being assessed in three investigational imaging trials MPDL3280A-img-042015, 89Zr-CD8 imaging or IL2-img--UMCG-2015.

To be able to evaluate the investigational imaging - 89Zr-MPDL3280A-PET, 89Zr-CD8 imaging and 18F-FB-IL2-PET - as complementary tools for selection of patients to be treated with MPDL3280A, within this treatment trial we will assess safety, tolerability and anti-tumor activity of MPDL3280A in cancer patients, who have undergone investigational imaging. Acquired data could lead to improved, more patient friendly, more easily accessible and possibly less expensive procedures for patient selection. Subsequently, the efficacy of (combinations of) checkpoint inhibition could also be improved, thus preventing unnecessary toxicity and reducing health care costs.

Being tested
MPDL3280A
Keywords
MPDL3280A, solid tumors

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MPDL3280ADrug

    Anti-PD-L1 antibody

Study groups in NCT02478099
Study groupRoleWhat they receive
1 Treatment with MPDL3280AExperimentalTreatment with MPDL3280A
Receives: Drug: MPDL3280A

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Evaluation of efficacy of MPDL3280A after investigational imaging as measured by objective response rate

    Measured: 2 years

Secondary outcomes (10)

  1. To evaluate progression free survival (PFS) according to standard RECIST v1.1 as assessed by the investigator.

    Measured: 2 years

  2. To evaluate duration of response (DOR) according to standard RECIST v1.1 as assessed by the investigator.

    Measured: 2 years

  3. To evaluate DOR according to modified RECIST as assessed by the investigator.

    Measured: 2 years

  4. To evaluate ORR according to modified RECIST as assessed by the investigator.

    Measured: 2 years

  5. To evaluate PFS according to modified RECIST as assessed by the investigator.

    Measured: 2 years

  6. To evaluate the safety/tolerability (by analysis of adverse events) of MPDL3280A.

    Safety assessment through:

    • Incidence, nature and severity of adverse events, including protocol-defined events of special interest, graded according to NCI CTCAE4.0
    • Changes in laboratory test results, vital signs and physical findings.

    Measured: 2 years

  7. To determine the number of patients with and patients without tumor tracer uptake with 89Zr-MPDL3280A,89Zr-CD8 antibody study and 18F-FB-IL2 (as assessed in the accessory imaging trials) who also demonstrate response to MPDL3280A therapy.

    Measured: 2 years

  8. To correlate PD-L1 biopsy results as assessed in the trials MPDL3280A-img-042015, 89Zr-CD8 antibody imaging and IL2-img-UMCG-2015 to response to MPDL3280A therapy.

    Measured: 2 years

  9. To evaluate the utility of biopsy at the time of apparent disease progression to distinguish apparent increases in tumor volume related to the immunomodulatory activity of MPDL3280A from true disease progression

    Measured: 2 years

  10. The fecal microbiome will be analysed in related to antitumor effect. Feces sampling will be performed before treatment and at cycle three.

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Jun 2015 (estimated)
  2. Study start24 Feb 2016
  3. Primary completion19 Sep 2023
  4. Study completionJul 2024 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
81 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02478099
Sponsor's protocol ID
ML29755
Status last verified
May 2024
First submitted
21 May 2015
Last updated
3 May 2024
Results posted
No
Data monitoring committee
No

Publications

  • Hooiveld-Noeken JS, van de Donk PP, Kist de Ruijter L, Kok IC, van Winkel CAJ, Giesen D, Lub-de Hooge MN, Brouwers AH, Oosting SF, Bensch F, Smit LM, Schroder CP, Jalving M, Elias SG, Gietema JA, Deurloo RJ, Williams SP, Ungewickell A, de Groot DA, de Vries EGE. Programmed death ligand 1 (PD-L1) PET/CT imaging to evaluate tumour saturation during atezolizumab treatment. Br J Cancer. 2026 Sep 10. doi: 10.1038/s41416-026-03595-8. Online ahead of print.

    PubMed 42722782

  • Bensch F, van der Veen EL, Lub-de Hooge MN, Jorritsma-Smit A, Boellaard R, Kok IC, Oosting SF, Schroder CP, Hiltermann TJN, van der Wekken AJ, Groen HJM, Kwee TC, Elias SG, Gietema JA, Bohorquez SS, de Crespigny A, Williams SP, Mancao C, Brouwers AH, Fine BM, de Vries EGE. 89Zr-atezolizumab imaging as a non-invasive approach to assess clinical response to PD-L1 blockade in cancer. Nat Med. 2018 Dec;24(12):1852-1858. doi: 10.1038/s41591-018-0255-8. Epub 2018 Nov 26.

    PubMed 30478423

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing MPDL3280A in people with Locally Advanced or Metastatic Solid Tumors, run by University Medical Center Groningen at 1 site in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 29 inclusion and 50 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 3 May 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Evaluation of efficacy of MPDL3280A after investigational imaging as measured by objective response rate (time frame: 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02478099, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 May 2024.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in